title: The cell-surface form of colony-stimulating factor-1 is regulated by osteotropic agents and supports formation of multinucleated osteoclast-like cells.
abstract: Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor that is released by osteoblasts and is recognized to play a critical role in bone remodeling in vivo and in vitro. CSF-1 is synthesized as a soluble or cell-surface protein. It is unclear, however, whether human osteoblasts express both molecular forms of CSF-1, and whether these isoforms can independently mediate osteoclastogenesis. In the present study, using a combination of quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and Western immunoblot analysis, we have demonstrated that human osteoblast-like cells as well as primary human osteoblasts express the cell-surface form of CSF-1 both constitutively and in response to parathyroid hormone and tumor necrosis factor. Furthermore, using an in vitro co-culture system, we have shown that cell-surface CSF-1 alone is sufficient to support osteoclast formation. These findings may be especially significant in view of evidence that direct cell-to-cell contact is critical for osteoclast formation, and suggest that differential regulation of expression of the CSF-1 isoforms may influence osteoclast function modulated by osteotropic hormones.
authors.affiliation: Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: G Q
authors.initials: GQ
authors.lastname: Yao
authors.forename: B h
authors.initials: Bh
authors.lastname: Sun
authors.forename: E E
authors.initials: EE
authors.lastname: Hammond
authors.forename: E N
authors.initials: EN
authors.lastname: Spencer
authors.forename: M C
authors.initials: MC
authors.lastname: Horowitz
authors.forename: K L
authors.initials: KL
authors.lastname: Insogna
authors.forename: E C
authors.initials: EC
authors.lastname: Weir
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006651:Histocytochemistry; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D008565:Membrane Proteins; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor